Evidence map›Paper›PMID 42286461›Full record

ArticleBMC bioinformatics2026

Protein language models are accidental taxonomists.

Logan Hallee, Tamar Peleg, Nikolaos Rafailidis, Jason P Gleghorn

Abstract read
In one paragraph

Article in BMC bioinformatics, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

4 authors.

Logan HalleeCenter for Bioinformatics and Computational Biology, University of Delaware, 590 Avenue 1743, Newark, DE, 19713, USA.
Tamar PelegDepartment of Medical and Molecular Sciences, University of Delaware, Willard E. Hall Education Bldg, 16 W Main St Suite 305, Newark, DE, 19716, USA.
Nikolaos RafailidisCenter for Bioinformatics and Computational Biology, University of Delaware, 590 Avenue 1743, Newark, DE, 19713, USA.
Jason P GleghornCenter for Bioinformatics and Computational Biology, University of Delaware, 590 Avenue 1743, Newark, DE, 19713, USA. gleghorn@udel.edu.

Funding

Practical Data-Centric AI/ML for Biomedical ResearchersT32GM142603 · NIGMS · UNIVERSITY OF DELAWARE · PI Shawn W Polson, Abhyudai Singh · 2022 to 2026
$1.4M
Dissecting the Protective Role of Cardiac Hsp90ß Ablation/InhibitionR01HL178817 · NHLBI · UNIVERSITY OF DELAWARE · PI Chi Keung Lam · 2025 to 2026
$1.2M
National Science Foundation NAIRR 240064NHLBI NIH HHS R01 HL178817NHLBI NIH HHS R01HL178817NIGMS NIH HHS T32 GM142603NIGMS NIH HHS T32GM142603
6 · The paper itself

Abstract

Protein-protein interactions (PPIs) are fundamental to nearly all biological processes, yet their experimental characterization remains costly and time-consuming. While computational methods, particularly those using protein language models (pLMs), offer higher-throughput solutions, they often report unexpectedly high performance on multi-species datasets. Here, we introduce the accidental taxonomist hypothesis, proposing that neural networks can exploit the phylogenetic distances across labels in protein datasets rather than genuine interaction features. We show that in standard multi-species PPI datasets, positive pairs typically share a taxonomic origin, while randomly sampled negatives do not. We then demonstrate that pLM embeddings can be used to accurately distinguish whether two proteins share a taxonomic origin, allowing models to "cheat" by learning phylogeny instead of genuine PPI features. By employing a strategic sampling strategy that restricts negative examples to protein pairs from the same species, we reveal a marked drop in model performance, confirming our hypothesis. Compellingly, these strategically trained models still outperform single-species models, suggesting that multi-species data can improve performance if carefully curated. These findings suggest that accidental taxonomist behavior is a particularly influential confounder for PPI, and it is also broadly applicable to any supervised-learning protein dataset.

Indexed as

Computational BiologyNeural Networks, ComputerProtein Interaction MappingProteinsDatabases, ProteinPhylogenyProteinsConfoundersNegative samplingPhylogeneticsProtein language modelingProtein-protein interactionsReward hackingTaxonomy

Identifiers

PMID42286461
PMCPMC13487993

What OpenQuestion holds

Textmetadata
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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.